ActRIIA and BMPRII Type II BMP Receptor Subunits Selectively Required for Smad4-Independent BMP7-Evoked Chemotaxis

Abstract

Bone morphogenetic protein (BMP)-evoked reorientation and chemotaxis of cells occurs with rapid onset and involves events local to the cell membrane. The signaling pathways underlying these rapid processes likely diverge from those mediating classical transcriptional responses to BMPs but it remains unclear how BMP receptors are utilized to generate distinct intracellular mechanisms. We show that BMP7-evoked chemotaxis of monocytic cells depends on the activity of canonical type II BMP receptors. Although the three canonical type II BMP receptors are expressed in monocytic cells, inhibition of receptor subunit expression by RNAi reveals that ActRIIA and BMPRII, but not ActRIIB, are each essential for BMP7-evoked chemotaxis but not required individually for BMP-mediated induction. Furthermore, the chemotactic response to BMP7 does not involve canonical Smad4-dependent signaling but acts through PI3K-dependent signaling, illustrating selective activation of distinct intracellular events through differential engagement of receptors. We suggest a model of a BMP receptor complex in which the coordinated activity of ActRIIA and BMPRII receptor subunits selectively mediates the chemotactic response to BMP7.

Appropriate Bmp7 levels are required for the differentiation of midline guidepost cells involved in corpus callosum formation

“…To our knowledge, a role of Bmp7 in the regulation of neuronal migration has not been reported before. However, BMP7-mediated chemotactic and inhibitory functions in cell migration have been reported in other systems, including melanomas, osteoblasts and monocytic cell lines (Lee et al, 2006;Na et al, 2009;Perron and Dodd, 2009). …”

Nodal·Gdf1 Heterodimers with Bound Prodomains Enable Serum-independent Nodal Signaling and Endoderm Differentiation

“…RNAi of Type II Receptors in Reporter Cells-The sequences of previously validated siRNAs against ACVR2B and BMPR2 were as described (34,35). On day 0, H-CrCR reporter cells were seeded in a 24-well plate (2.5 ϫ 10 4 /well).…”

“…Nodal signaling in utero is mediated by complexes of ACVR1B To directly assess the effects of different type II receptors on Nodal versus Nodal⅐Gdf1 signaling, we transfected H-CrCR reporter cells with established siRNAs (34,35). Depletion of 70% of ACVR2B mRNA in H-CrCR cells reduced the induction of CAGA-luc by recombinant Nodal to less than 30% (Fig.…”

BMP-6 in Renal Cell Carcinoma Promotes Tumor Proliferation through IL-10–Dependent M2 Polarization of Tumor-Associated Macrophages

“…Although originally reported as factors that induce bone and cartilage formation (3), BMPs have been shown to be critical for development (4)(5)(6). More recently, we and others have reported that BMPs regulate the immune system as BMP-6 inhibits B-and T-cell proliferation (7,8) and activates macrophages (9,10).…”